Prenatal Exposure to DEHTP Replacement Metabolites and Odds of Preeclampsia and Gestational Hypertension in a Diverse Nulliparous U.S. Cohort

Background Prenatal exposure to phthalate metabolites is associated with adverse pregnancy outcomes (APOs); however, it is unknown whether replacement phthalate compounds, such as di-2-ethylhexyl terephthalate (DEHTP), are safer alternatives. Methods We examined associations between prenatal exposure to phthalate metabolites, replacement phthalate metabolites, and APOs using data from a nested case-control study (n = 2,040) within the Nulliparous Pregnancy Outcomes Study: Monitoring Mothers-to-Be cohort. Cases included 1,020 participants with preeclampsia (PE), new-onset gestational hypertension (GHTN), or spontaneous preterm birth (sPTB), matched 1:1 to controls by clinical site, maternal age, and infant sex. Twelve phthalate metabolites, including DEHTP metabolites mono-2-ethyl-5-carboxypentyl terephthalate (MECPTP) and mono-2-ethyl-5-hydroxyhexyl terephthalate (MEHHTP), were measured in urine samples across pregnancy (total = 5,265). We used multivariable conditional logistic regression to evaluate associations between specific gravity-adjusted geometric mean metabolite concentrations and each outcome, with metabolites modeled by quartiles and continuously. Infant sex and self-reported race and ethnicity were a priori effect measure modifiers. Results Higher concentrations of MEHHTP increased the overall odds of PE (adjusted OR [aOR], highest vs. lowest quartile: 1.90; 95% CI: 1.07–3.36). MECPTP was most strongly associated with PE among participants carrying infant girls (aOR, highest vs. lowest quartile: 6.49; 95% CI: 2.03–18.43), and with GHTN among non-Hispanic White participants (aOR, highest vs. lowest quartile: 2.50; 95% CI: 1.17–5.36). Conclusion These results indicate that prenatal exposure to DEHTP metabolites may be associated with APOs, specifically PE, and highlight the need for continued research and monitoring of these replacement compounds.